Krüppel is a gap gene in Drosophila melanogaster, located on the 2R chromosome, which encodes a zinc finger C2H2 transcription factor.[1][2] Gap genes work together to establish the anterior-posterior segment patterning of the insect through regulation of the transcription factor encoding pair rule genes. These genes in turn regulate segment polarity genes.[3]Krüppel means "cripple" in German, named for the crippled appearance of mutant larvae, who have failed to develop proper thoracic and anterior segments in the abdominal region.[4][5][6] Mutants can also have abdominal mirror duplications.
In situ hybridization against mRNA of the gap genes knirps, Krüppel and giant in the Drosophila melanogaster early embryo. Panels also show how these genes are affected by the mutation brakeless (bks).
Krüppel is expressed in the center of the embryo during the cellular blastoderm stage of development.[12] Its expression pattern is restricted to this domain largely through interactions with the maternal effect genes Bicoid and Nanos, and fellow gap gene Hunchback and Knirps.[13]
Bicoid maternal transcripts are deposited at the anterior end of the embryo, while Nanos maternal transcripts are located at the posterior. Hunchback mRNA transcripts are present throughout the embryo. Bicoid and Nanos both encode morphogens that have the opposite effect on Hunchback mRNA translation – Bicoid activates translation, whereas Nanos represses it.[14] As such, Hunchback mRNA is translated so that Hunchback protein is present in the concentration gradient which decreases along the anterior – posterior axis. This Hunchback gradient indirectly results in an anterior boundary for Knirps expression. Other factors induce a posterior boundary, so that Knirps is expressed in a stripe in the posterior region of the embryo.
Hunchback and Knirps are both transcription factors that regulate Krüppel expression. High levels of Hunchback inhibit expression, whereas low levels of Hunchback activate expression. Knirps acts as a repressor to inhibit expression. This results in Krüppel being expressed in a stripe in the center of the embryo's A-P axis, where Hunchback concentration has dropped to a low enough level so that it can act as an activator, but Knirps is not yet present to inhibit. In this way the initial gradients of morphogens can lead to the establishment of a specific region within the blastoderm. It can be compared to a narrow bandwidth filter in engineering.
Effects of Krüppel expressionedit
The Krüppel protein is a transcription factor, and has been shown to act as a repressor. It functions in collaboration with other gap genes and their localized protein products to regulate the expression of the primary pair rule genes – even skipped (eve), hairy (h), and runt.[15] It has been postulated that Krüppel inhibits eve expression to create the posterior boundary of eve stripe two, and evidence has also been found for Krüppel being a player specifically in the formation of hairy stripe 7.[16][17] The expression patterns of pair rule gene will in turn regulate the segment polarity genes, making Krüppel essential for proper development along the anterior posterior axis and segment identity.
^Kinzler KW, Ruppert JM, Bigner SH, Vogelstein B (March 1988). "The GLI gene is a member of the Kruppel family of zinc finger proteins". Nature. 332 (6162): 371–4. Bibcode:1988Natur.332..371K. doi:10.1038/332371a0. PMID 2832761. S2CID 4279828.
^Hoy MA (January 2019). "Genetic Systems, Genome Evolution, and Genetic Control of Embryonic Development in Insects". In Hoy MA (ed.). Insect Molecular Genetics. Academic Press. pp. 103–175. doi:10.1016/B978-0-12-815230-0.00004-2. ISBN9780128152300. {{cite book}}: |work= ignored (help)
^Nüsslein-Volhard C, Wieschaus E (October 1980). "Mutations affecting segment number and polarity in Drosophila". Nature. 287 (5785): 795–801. Bibcode:1980Natur.287..795N. doi:10.1038/287795a0. PMID 6776413. S2CID 4337658.
^Nüsslein-Volhard C, Wieschaus E, Kluding H (September 1984). "Mutations affecting the pattern of the larval cuticle inDrosophila melanogaster : I. Zygotic loci on the second chromosome". Wilhelm Roux's Archives of Developmental Biology. 193 (5): 267–282. doi:10.1007/BF00848156. PMID 28305337. S2CID 2195415.
^Wieschaus E, Nusslein-Volhard C, Kluding H (July 1984). "Krüppel, a gene whose activity is required early in the zygotic genome for normal embryonic segmentation". Developmental Biology. 104 (1): 172–86. doi:10.1016/0012-1606(84)90046-0. PMID 6428949.
^Schuh R, Aicher W, Gaul U, Côté S, Preiss A, Maier D, et al. (December 1986). "A conserved family of nuclear proteins containing structural elements of the finger protein encoded by Krüppel, a Drosophila segmentation gene". Cell. 47 (6): 1025–32. doi:10.1016/0092-8674(86)90817-2. PMID 3096579.
^Yori JL, Seachrist DD, Johnson E, Lozada KL, Abdul-Karim FW, Chodosh LA, et al. (July 2011). "Krüppel-like factor 4 inhibits tumorigenic progression and metastasis in a mouse model of breast cancer". Neoplasia. 13 (7): 601–10. doi:10.1593/neo.11260. PMC3132846. PMID 21750654.
^Lin ZS, Chu HC, Yen YC, Lewis BC, Chen YW (2012). "Krüppel-like factor 4, a tumor suppressor in hepatocellular carcinoma cells reverts epithelial mesenchymal transition by suppressing slug expression". PLOS ONE. 7 (8): e43593. Bibcode:2012PLoSO...743593L. doi:10.1371/journal.pone.0043593. PMC3427336. PMID 22937066.
^Wei D, Gong W, Kanai M, Schlunk C, Wang L, Yao JC, et al. (April 2005). "Drastic down-regulation of Krüppel-like factor 4 expression is critical in human gastric cancer development and progression". Cancer Research. 65 (7): 2746–54. doi:10.1158/0008-5472.CAN-04-3619. PMID 15805274.
^Lee UE, Ghiassi-Nejad Z, Paris AJ, Yea S, Narla G, Walsh M, Friedman SL (March 2010). "Tumor suppressor activity of KLF6 mediated by downregulation of the PTTG1 oncogene". FEBS Letters. 584 (5): 1006–10. doi:10.1016/j.febslet.2010.01.049. PMC2827621. PMID 20116377.
^Licht JD, Grossel MJ, Figge J, Hansen UM (July 1990). "Drosophila Krüppel protein is a transcriptional repressor". Nature. 346 (6279): 76–9. Bibcode:1990Natur.346...76L. doi:10.1038/346076a0. PMID 2114551. S2CID 10301966.
^Knipple DC, Seifert E, Rosenberg UB, Preiss A, Jäckle H (1985). "Spatial and temporal patterns of Krüppel gene expression in early Drosophila embryos". Nature. 317 (6032): 40–4. Bibcode:1985Natur.317...40K. doi:10.1038/317040a0. PMID 2412131. S2CID 4340589.
^Porcher A, Dostatni N (March 2010). "The bicoid morphogen system". Current Biology. 20 (5): R249-54. doi:10.1016/j.cub.2010.01.026. PMID 20219179.
^Pankratz MJ, Seifert E, Gerwin N, Billi B, Nauber U, Jäckle H (April 1990). "Gradients of Krüppel and knirps gene products direct pair-rule gene stripe patterning in the posterior region of the Drosophila embryo". Cell. 61 (2): 309–17. doi:10.1016/0092-8674(90)90811-R. PMID 2331752. S2CID 44716994.
^Small S, Kraut R, Hoey T, Warrior R, Levine M (May 1991). "Transcriptional regulation of a pair-rule stripe in Drosophila". Genes & Development. 5 (5): 827–39. doi:10.1101/gad.5.5.827. PMID 2026328.
^La Rosée-Borggreve A, Häder T, Wainwright D, Sauer F, Jäckle H (December 1999). "hairy stripe 7 element mediates activation and repression in response to different domains and levels of Krüppel in the Drosophila embryo". Mechanisms of Development. 89 (1–2): 133–40. doi:10.1016/s0925-4773(99)00219-1. hdl:11858/00-001M-0000-002A-18E2-F. PMID 10559488. S2CID 17728959.
^Ghaleb AM, Katz JP, Kaestner KH, Du JX, Yang VW (April 2007). "Krüppel-like factor 4 exhibits antiapoptotic activity following gamma-radiation-induced DNA damage". Oncogene. 26 (16): 2365–73. doi:10.1038/sj.onc.1210022. PMC2230633. PMID 17016435.
^Brey CW, Nelder MP, Hailemariam T, Gaugler R, Hashmi S (October 2009). "Krüppel-like family of transcription factors: an emerging new frontier in fat biology". International Journal of Biological Sciences. 5 (6): 622–36. doi:10.7150/ijbs.5.622. PMC2757581. PMID 19841733.
^Hamik A, Lin Z, Kumar A, Balcells M, Sinha S, Katz J, et al. (May 2007). "Kruppel-like factor 4 regulates endothelial inflammation". The Journal of Biological Chemistry. 282 (18): 13769–79. doi:10.1074/jbc.M700078200. PMID 17339326.
^Rajamannan NM, Subramaniam M, Abraham TP, Vasile VC, Ackerman MJ, Monroe DG, et al. (February 2007). "TGFbeta inducible early gene-1 (TIEG1) and cardiac hypertrophy: Discovery and characterization of a novel signaling pathway". Journal of Cellular Biochemistry. 100 (2): 315–25. doi:10.1002/jcb.21049. PMC3927779. PMID 16888812.
^Jiang J, Chan YS, Loh YH, Cai J, Tong GQ, Lim CA, et al. (March 2008). "A core Klf circuitry regulates self-renewal of embryonic stem cells". Nature Cell Biology. 10 (3): 353–60. doi:10.1038/ncb1698. PMID 18264089. S2CID 22150633.
^Nandan MO, Yang VW (October 2009). "The role of Krüppel-like factors in the reprogramming of somatic cells to induced pluripotent stem cells". Histology and Histopathology. 24 (10): 1343–55. doi:10.14670/HH-24.1343. PMC2753264. PMID 19688699.
^Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (November 2007). "Induction of pluripotent stem cells from adult human fibroblasts by defined factors". Cell. 131 (5): 861–72. doi:10.1016/j.cell.2007.11.019. hdl:2433/49782. PMID 18035408. S2CID 8531539.
External linksedit
Diagram at Davidson College - a Drosophila embryo at the cellular blastoderm stage triple-labeled for three segmentation proteins including Krüppel (in blue) Hairy (green) and Giant (red).
Kruppel+protein,+Drosophila at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
February 26, 2024
krüppel, gene, drosophila, melanogaster, located, chromosome, which, encodes, zinc, finger, c2h2, transcription, factor, genes, work, together, establish, anterior, posterior, segment, patterning, insect, through, regulation, transcription, factor, encoding, p. Kruppel is a gap gene in Drosophila melanogaster located on the 2R chromosome which encodes a zinc finger C2H2 transcription factor 1 2 Gap genes work together to establish the anterior posterior segment patterning of the insect through regulation of the transcription factor encoding pair rule genes These genes in turn regulate segment polarity genes 3 Kruppel means cripple in German named for the crippled appearance of mutant larvae who have failed to develop proper thoracic and anterior segments in the abdominal region 4 5 6 Mutants can also have abdominal mirror duplications KruppelIdentifiersOrganismDrosophila melanogasterSymbolkrUniProtP07247Search forStructuresSwiss modelDomainsInterProKruppel homolog 1IdentifiersOrganismDrosophila melanogasterSymbolkr h1UniProtP08155Search forStructuresSwiss modelDomainsInterProKruppel homolog 2IdentifiersOrganismDrosophila melanogasterSymbolkr h2UniProtQ9V447Search forStructuresSwiss modelDomainsInterProKruppel like factor lunaIdentifiersOrganismDrosophila melanogasterSymbollunaUniProtQ8MR37Search forStructuresSwiss modelDomainsInterProIn situ hybridization against mRNA of the gap genes knirps Kruppel and giant in the Drosophila melanogaster early embryo Panels also show how these genes are affected by the mutation brakeless bks Human homologs of Kruppel are collectively named Kruppel like factors a set of proteins well characterized for their role in carcinogenesis 7 8 9 10 11 Contents 1 Kruppel expression pathway 2 Effects of Kruppel expression 3 Clinical significance 4 See also 5 References 6 External linksKruppel expression pathway editKruppel is expressed in the center of the embryo during the cellular blastoderm stage of development 12 Its expression pattern is restricted to this domain largely through interactions with the maternal effect genes Bicoid and Nanos and fellow gap gene Hunchback and Knirps 13 Bicoid maternal transcripts are deposited at the anterior end of the embryo while Nanos maternal transcripts are located at the posterior Hunchback mRNA transcripts are present throughout the embryo Bicoid and Nanos both encode morphogens that have the opposite effect on Hunchback mRNA translation Bicoid activates translation whereas Nanos represses it 14 As such Hunchback mRNA is translated so that Hunchback protein is present in the concentration gradient which decreases along the anterior posterior axis This Hunchback gradient indirectly results in an anterior boundary for Knirps expression Other factors induce a posterior boundary so that Knirps is expressed in a stripe in the posterior region of the embryo Hunchback and Knirps are both transcription factors that regulate Kruppel expression High levels of Hunchback inhibit expression whereas low levels of Hunchback activate expression Knirps acts as a repressor to inhibit expression This results in Kruppel being expressed in a stripe in the center of the embryo s A P axis where Hunchback concentration has dropped to a low enough level so that it can act as an activator but Knirps is not yet present to inhibit In this way the initial gradients of morphogens can lead to the establishment of a specific region within the blastoderm It can be compared to a narrow bandwidth filter in engineering Effects of Kruppel expression editThe Kruppel protein is a transcription factor and has been shown to act as a repressor It functions in collaboration with other gap genes and their localized protein products to regulate the expression of the primary pair rule genes even skipped eve hairy h and runt 15 It has been postulated that Kruppel inhibits eve expression to create the posterior boundary of eve stripe two and evidence has also been found for Kruppel being a player specifically in the formation of hairy stripe 7 16 17 The expression patterns of pair rule gene will in turn regulate the segment polarity genes making Kruppel essential for proper development along the anterior posterior axis and segment identity Clinical significance editKruppel has shown homology to the mammalian Kruppel like factors which play key biological roles in the pathogenesis of many human diseases cancer 18 obesity 19 inflammatory disorders 20 and cardiovascular complications 21 Moreover KLFs are known to be involved in inducible pluripotent stem cells generation and preservation of the pluripotent state of embryonic stem cells 22 23 24 See also editDrosophila melanogaster Drosophila embryogenesis Maternal effectReferences edit Kinzler KW Ruppert JM Bigner SH Vogelstein B March 1988 The GLI gene is a member of the Kruppel family of zinc finger proteins Nature 332 6162 371 4 Bibcode 1988Natur 332 371K doi 10 1038 332371a0 PMID 2832761 S2CID 4279828 FlyBase Gene Report Dmel Kr flybase org Retrieved 2019 10 08 Hoy MA January 2019 Genetic Systems Genome Evolution and Genetic Control of Embryonic Development in Insects In Hoy MA ed Insect Molecular Genetics Academic Press pp 103 175 doi 10 1016 B978 0 12 815230 0 00004 2 ISBN 9780128152300 a href Template Cite book html title Template Cite book cite book a work ignored help Nusslein Volhard C Wieschaus E October 1980 Mutations affecting segment number and polarity in Drosophila Nature 287 5785 795 801 Bibcode 1980Natur 287 795N doi 10 1038 287795a0 PMID 6776413 S2CID 4337658 Nusslein Volhard C Wieschaus E Kluding H September 1984 Mutations affecting the pattern of the larval cuticle inDrosophila melanogaster I Zygotic loci on the second chromosome Wilhelm Roux s Archives of Developmental Biology 193 5 267 282 doi 10 1007 BF00848156 PMID 28305337 S2CID 2195415 Wieschaus E Nusslein Volhard C Kluding H July 1984 Kruppel a gene whose activity is required early in the zygotic genome for normal embryonic segmentation Developmental Biology 104 1 172 86 doi 10 1016 0012 1606 84 90046 0 PMID 6428949 Schuh R Aicher W Gaul U Cote S Preiss A Maier D et al December 1986 A conserved family of nuclear proteins containing structural elements of the finger protein encoded by Kruppel a Drosophila segmentation gene Cell 47 6 1025 32 doi 10 1016 0092 8674 86 90817 2 PMID 3096579 Yori JL Seachrist DD Johnson E Lozada KL Abdul Karim FW Chodosh LA et al July 2011 Kruppel like factor 4 inhibits tumorigenic progression and metastasis in a mouse model of breast cancer Neoplasia 13 7 601 10 doi 10 1593 neo 11260 PMC 3132846 PMID 21750654 Lin ZS Chu HC Yen YC Lewis BC Chen YW 2012 Kruppel like factor 4 a tumor suppressor in hepatocellular carcinoma cells reverts epithelial mesenchymal transition by suppressing slug expression PLOS ONE 7 8 e43593 Bibcode 2012PLoSO 743593L doi 10 1371 journal pone 0043593 PMC 3427336 PMID 22937066 Wei D Gong W Kanai M Schlunk C Wang L Yao JC et al April 2005 Drastic down regulation of Kruppel like factor 4 expression is critical in human gastric cancer development and progression Cancer Research 65 7 2746 54 doi 10 1158 0008 5472 CAN 04 3619 PMID 15805274 Lee UE Ghiassi Nejad Z Paris AJ Yea S Narla G Walsh M Friedman SL March 2010 Tumor suppressor activity of KLF6 mediated by downregulation of the PTTG1 oncogene FEBS Letters 584 5 1006 10 doi 10 1016 j febslet 2010 01 049 PMC 2827621 PMID 20116377 Licht JD Grossel MJ Figge J Hansen UM July 1990 Drosophila Kruppel protein is a transcriptional repressor Nature 346 6279 76 9 Bibcode 1990Natur 346 76L doi 10 1038 346076a0 PMID 2114551 S2CID 10301966 Knipple DC Seifert E Rosenberg UB Preiss A Jackle H 1985 Spatial and temporal patterns of Kruppel gene expression in early Drosophila embryos Nature 317 6032 40 4 Bibcode 1985Natur 317 40K doi 10 1038 317040a0 PMID 2412131 S2CID 4340589 Porcher A Dostatni N March 2010 The bicoid morphogen system Current Biology 20 5 R249 54 doi 10 1016 j cub 2010 01 026 PMID 20219179 Pankratz MJ Seifert E Gerwin N Billi B Nauber U Jackle H April 1990 Gradients of Kruppel and knirps gene products direct pair rule gene stripe patterning in the posterior region of the Drosophila embryo Cell 61 2 309 17 doi 10 1016 0092 8674 90 90811 R PMID 2331752 S2CID 44716994 Small S Kraut R Hoey T Warrior R Levine M May 1991 Transcriptional regulation of a pair rule stripe in Drosophila Genes amp Development 5 5 827 39 doi 10 1101 gad 5 5 827 PMID 2026328 La Rosee Borggreve A Hader T Wainwright D Sauer F Jackle H December 1999 hairy stripe 7 element mediates activation and repression in response to different domains and levels of Kruppel in the Drosophila embryo Mechanisms of Development 89 1 2 133 40 doi 10 1016 s0925 4773 99 00219 1 hdl 11858 00 001M 0000 002A 18E2 F PMID 10559488 S2CID 17728959 Ghaleb AM Katz JP Kaestner KH Du JX Yang VW April 2007 Kruppel like factor 4 exhibits antiapoptotic activity following gamma radiation induced DNA damage Oncogene 26 16 2365 73 doi 10 1038 sj onc 1210022 PMC 2230633 PMID 17016435 Brey CW Nelder MP Hailemariam T Gaugler R Hashmi S October 2009 Kruppel like family of transcription factors an emerging new frontier in fat biology International Journal of Biological Sciences 5 6 622 36 doi 10 7150 ijbs 5 622 PMC 2757581 PMID 19841733 Hamik A Lin Z Kumar A Balcells M Sinha S Katz J et al May 2007 Kruppel like factor 4 regulates endothelial inflammation The Journal of Biological Chemistry 282 18 13769 79 doi 10 1074 jbc M700078200 PMID 17339326 Rajamannan NM Subramaniam M Abraham TP Vasile VC Ackerman MJ Monroe DG et al February 2007 TGFbeta inducible early gene 1 TIEG1 and cardiac hypertrophy Discovery and characterization of a novel signaling pathway Journal of Cellular Biochemistry 100 2 315 25 doi 10 1002 jcb 21049 PMC 3927779 PMID 16888812 Jiang J Chan YS Loh YH Cai J Tong GQ Lim CA et al March 2008 A core Klf circuitry regulates self renewal of embryonic stem cells Nature Cell Biology 10 3 353 60 doi 10 1038 ncb1698 PMID 18264089 S2CID 22150633 Nandan MO Yang VW October 2009 The role of Kruppel like factors in the reprogramming of somatic cells to induced pluripotent stem cells Histology and Histopathology 24 10 1343 55 doi 10 14670 HH 24 1343 PMC 2753264 PMID 19688699 Takahashi K Tanabe K Ohnuki M Narita M Ichisaka T Tomoda K Yamanaka S November 2007 Induction of pluripotent stem cells from adult human fibroblasts by defined factors Cell 131 5 861 72 doi 10 1016 j cell 2007 11 019 hdl 2433 49782 PMID 18035408 S2CID 8531539 External links editDiagram at Davidson College a Drosophila embryo at the cellular blastoderm stage triple labeled for three segmentation proteins including Kruppel in blue Hairy green and Giant red Kruppel protein Drosophila at the U S National Library of Medicine Medical Subject Headings MeSH Retrieved from https en wikipedia org w index php title Kruppel amp oldid 1193580992, wikipedia, wiki, book, books, library,
